Open AccessIncreased Expression of the Normal Cellular Isoform of Prion Protein in Inclusion‐Body Myositis, Inflammatory Myopathies and Denervation Atrophy
Author(s) -
Zanusso Gianluigi,
Vattemi Gaetano,
Ferrari Sergio,
Tabaton Massimo,
Pecini Elisa,
Cavallaro Tiziana,
Tomelleri Giuliano,
Filosto Massimiliano,
Tonin Paola,
Nardelli Ettore,
Rizzuto Nicola,
Monaco Salvatore
Publication year - 2001
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/j.1750-3639.2001.tb00390.x
Subject(s) - inclusion body myositis , gene isoform , polymyositis , myositis , scrapie , myopathy , denervation , atrophy , muscle atrophy , pathology , skeletal muscle , dermatomyositis , neurodegeneration , biology , chemistry , biochemistry , prion protein , immunology , endocrinology , disease , medicine , gene
The cellular isoform of the prion protein (PrP c ) is a glycosylphosphatidylinositol‐anchored glycoprotein, normally expressed in neural and non‐neural tissues, including skeletal muscle. In transmissible spongiform encephalopathies, or prion diseases, PrP c , which is soluble in nondenaturing detergent and sensitive to proteinase K (PK)‐treatment, represents the molecular substrate for the production of a detergent‐insoluble and PK‐resistant isoform, termed PrP Sc . In human prion diseases, PrP Sc accumulation occurs only in brain tissues, with the exception of new variant Creutzfeldt‐Jakob disease, where PrP Sc is also detected in lymphoid tissues. Increased amounts of prion protein expression and deposition have been described in pathological muscle fibers of two human muscle disorders, called sporadic inclusion‐body myositis (s‐IBM) and hereditary inclusion‐body myopathy, but it is unknown whether accumulated prion protein reflects normal PrP c or PrP Sc . We investigated the biochemical characteristics of prion protein in normal human muscle, s‐IBM, other inflammatory myopathies and denervation atrophy. We report that 1 ) both the glycoform profile and size of the normal muscle PrP c are different from those of human brain PrP c ; 2 ) in addition to s‐IBM, increased PrP c expression is seen in polymyositis, dermatomyositis and neurogenic muscle atrophy, but PrP c glycoforms are unchanged; 3 ) only the normal PrP c isoform, and not PrP Sc , is detected in s‐IBM. The present results exclude that s‐IBM is a prion disease.